Project Summary/Abstract Psychophysiological responses to stress may provide a means for identifying youth at high risk for substance use. The sympathetic nervous system (SNS) and parasympathetic nervous system (PNS)?the two branches of the autonomic nervous system?are two ideal physiological systems. They are both sensitive to social stress and reliably related to psychological constructs related to substance use: impulsivity and emotion regulation, respectively. Moreover, blunted SNS and PNS reactivity have been linked with poorer mental health in youth and greater substance use in adults. However, limited work has examined how stress reactivity relates to substance use during adolescence, which is especially critical given that substance use increases during this time and early substance use can increase risk for substance use disorders. This proposal aims to address this gap by analyzing how SNS and PNS reactivity to stress relate to substance use in adolescence using two data sets. First, in the CHAMACOS dataset, links will be tested between SNS and PNS reactivity?as well as cross- system profiles of responses?at age 14 and substance use at age 14 and 16. This analysis provides a robust test of utility of these physiological responses for identifying concurrent and prospective substance use during a period when substance use is rapidly increasing. Then, links between substance use and both physiological and affective reactivity to stress will be tested in the Study of Family Health. In addition to completing the stress paradigm, adolescents reported their mood and stressors experienced for 14 days through daily diaries. PNS reactivity may relate to substance use because PNS activity indexes capacity for emotion regulation, and poor emotion regulation can increase proclivity for substance use. This aim will assess how physiological responses to a validated stressor and psychological responses to ecological stressors relate to substance use and thereby provide insight regarding why physiological responses relate to substance use. Finally, sex differences in links between substance use and stress responses will be assessed in both datasets. Researchers have hypothesized that impulsivity and emotion regulation?and, by extension, their physiological correlates?relate to substance use differently in males and females. Results will further clarify whether sex influences adolescent substance use and whether interventions should be tailored differently for males and females. Taken together, findings from this proposal will assess the utility of SNS and PNS reactivity for concurrent (Aims 1 and 2) and prospective substance use (Aim 1), interrogate the psychological means by which PNS reactivity may relate to substance use (Aim 2), and explore sex differences in these patterns (Aim 3). This information can be used for identification of youth at higher risk for substance use, developing interventions (e.g., targeting biofeedback, emotion regulation), and tailoring these interventions to males and females. Moreover, they build on pre- existing hypotheses regarding sex differences in substance use and utilize a developmental perspective to extend present findings to adolescence, a period when this work can be especially impactful for health.